title: Key factors for successful generation of protein-fragment structures requirement on protein, crystals, and technology.
abstract: In the past two decades, fragment-based approaches have evolved as a predominant strategy in lead discovery. The availability of structural information on the interaction geometries of binding fragments is key to successful structure-guided fragment-to-lead evolution. In this chapter, we illustrate methodological advances for protein-fragment crystal structure generation in order to offer general lessons on the importance of fragment properties and the most appropriate crystallographic setup to evaluate them. We analyze elaborate protocols, methods, and clues applied to challenging complex formation projects. The results should assist medicinal chemists to select the most promising targets and strategies for fragment-based crystallography as well as provide a tutorial to structural biologists who attempt to determine protein-fragment structures.
authors.affiliation: Proteros biostructures GmbH, Am Klopferspitz 19, Martinsried, Germany.
authors.forename: Jark
authors.initials: J
authors.lastname: Böttcher
authors.forename: Anja
authors.initials: A
authors.lastname: Jestel
authors.forename: Reiner
authors.initials: R
authors.lastname: Kiefersauer
authors.forename: Stephan
authors.initials: S
authors.lastname: Krapp
authors.forename: Susanna
authors.initials: S
authors.lastname: Nagel
authors.forename: Stefan
authors.initials: S
authors.lastname: Steinbacher
authors.forename: Holger
authors.initials: H
authors.lastname: Steuber
mesh_terms: D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*
chemical_list: D008024:Ligands; D011506:Proteins